# Ciliary Defects in Inherited Retinal Diseases **Authors:** Guizhi Guo, Lin Li, Jun Zhou, Jie Ran PMC · DOI: 10.1002/ggn2.202500066 · 2026-03-06 ## TL;DR This review explains how defects in photoreceptor cilia cause inherited retinal diseases and explores new treatments targeting these defects. ## Contribution The paper systematically summarizes ciliary defects in IRDs and evaluates novel therapeutic strategies for ciliary restoration. ## Key findings - Ciliary gene mutations cause structural and functional defects in photoreceptor cilia, leading to inherited retinal diseases. - Emerging gene-targeted therapies show promise for treating ciliary defects in retinal degeneration. - Understanding molecular mechanisms of ciliary dysfunction is key to developing effective IRD treatments. ## Abstract Inherited retinal diseases (IRDs) are a heterogeneous group of disorders characterized by progressive photoreceptor degeneration that frequently results in severe vision loss. A major cause of IRDs is attributed to structural or functional defects of the photoreceptor cilium that arise from mutations in ciliary genes. The photoreceptor outer segment is a highly specialized sensory cilium composed of hundreds of stacked, flattened, membranous discs. This complex membrane architecture constitutes the primary site of phototransduction, in which light stimuli are converted into biochemical signaling cascades that ultimately generate electrical signals. In this review, the structure and function of photoreceptors are systematically described, major classes of IRDs caused by mutations in ciliary genes are summarized, and the therapeutic potential of emerging ciliary gene‐targeted strategies is critically evaluated in the context of recent advances in IRD treatment. The photoreceptor cilium is a specialized sensory organelle essential for vision. This review systematically summarizes the structural and functional defects of the cilium that lead to inherited retinal diseases (IRDs). It highlights key pathogenic genes, elucidates molecular mechanisms of degeneration, and evaluates emerging therapeutic strategies targeting ciliary restoration. ## Linked entities - **Diseases:** IRDs (MONDO:0009971) ## Full-text entities - **Genes:** ift88 (intraflagellar transport 88 homolog) [NCBI Gene 321855] {aka fb37b11, polaris, ttc10, wu:fb37b11, xx:zah8127}, Crb1 (crumbs family member 1, photoreceptor morphogenesis associated) [NCBI Gene 170788] {aka 7530426H14Rik, A930008G09Rik, CRB1-A, CRB1-A2, CRB1-B, CRB1-C}, Ush2a (usherin) [NCBI Gene 22283] {aka A930011D15Rik, A930037M10Rik, Gm676, Gm983, Mush2a, Ushrn}, rpgra (retinitis pigmentosa GTPase regulator a) [NCBI Gene 571327] {aka rpgr, si:dkey-19h21.4}, GUCY2D (guanylate cyclase 2D, retinal) [NCBI Gene 3000] {aka CACD, CACD1, CG-E, CORD5, CORD6, CSNB1I}, Prph2 (peripherin 2) [NCBI Gene 19133] {aka AOFMD, AVMD, Nmf193, PRPH, RP7, Rd-2}, Prom1 (prominin 1) [NCBI Gene 19126] {aka 4932416E19Rik, AC133, CD133, Prom, Prom-1, Proml1}, CEP290 (centrosomal protein 290) [NCBI Gene 80184] {aka 3H11Ag, BBS14, CT87, JBTS5, LCA10, MKS4}, Ahi1 (Abelson helper integration site 1) [NCBI Gene 52906] {aka 1700015F03Rik, Ahi-1, D10Bwg0629e}, vegfaa (vascular endothelial growth factor Aa) [NCBI Gene 30682] {aka vegf, vegfa, wu:fj82c06}, Myo7a (myosin VIIA) [NCBI Gene 17921] {aka Hdb, Myo7, USH1B, nmf371, polka, sh-1}, Tmem138 (transmembrane protein 138) [NCBI Gene 72982] {aka 1700113I01Rik, 2900055D14Rik}, Abca4 (ATP-binding cassette, sub-family A member 4) [NCBI Gene 11304] {aka Abc10, Abcr, D430003I15Rik, RmP}, rab8a (RAB8A, member RAS oncogene family) [NCBI Gene 571897] {aka rab8, zgc:162699}, cc2d2a (coiled-coil and C2 domain containing 2A) [NCBI Gene 570250] {aka fc03c12, wu:fc03c12}, Ift20 (intraflagellar transport 20) [NCBI Gene 55978] {aka 0610009H04Rik, mIFT20}, Gdf10 (growth differentiation factor 10) [NCBI Gene 79216], Ofd1 (OFD1, centriole and centriolar satellite protein) [NCBI Gene 237222] {aka Cxorf5, DXGgc7e, ORF2}, Wasf3 (WASP family, member 3) [NCBI Gene 245880] {aka Scar3, Wave3}, Spata7 (spermatogenesis associated 7) [NCBI Gene 104871] {aka B230306G18Rik, HSD3}, HDAC6 (histone deacetylase 6) [NCBI Gene 10013] {aka CPBHM, HD6, JM21, KDAC6, PPP1R90}, Bbs1 (Bardet-Biedl syndrome 1) [NCBI Gene 52028] {aka D19Ertd609e}, Rom1 (rod outer segment membrane protein 1) [NCBI Gene 19881] {aka M101156, Rgsc1156, Rom-1, Rosp1, Tspan23}, stx3b (syntaxin 3b) [NCBI Gene 393515] {aka stx3a, zgc:65954}, Kif3b (kinesin family member 3B) [NCBI Gene 16569] {aka mKIAA0359}, Rp2 (retinitis pigmentosa 2 homolog) [NCBI Gene 19889] {aka Rp2h}, Rp1 (retinitis pigmentosa 1 (human)) [NCBI Gene 19888] {aka Dcdc3, Gm38717, Orp1, Rp1h, mG145}, rho (rhodopsin) [NCBI Gene 30295] {aka RH1, Rh, rh1.1, wu:fi06d11, zfo2, zfrho}, Tmem216 (transmembrane protein 216) [NCBI Gene 68642] {aka 1110017C22Rik, 2810441K11Rik, 4921533J23Rik, A930021F15Rik}, Cep290 (centrosomal protein 290) [NCBI Gene 216274] {aka Nphp6, b2b1454Clo, b2b1752Clo}, RPE65 (retinoid isomerohydrolase RPE65) [NCBI Gene 6121] {aka BCO3, LCA2, RP20, mRPE65, p63, rd12}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, rab28 (RAB28, member RAS oncogene family) [NCBI Gene 326923] {aka wu:fe49e06, zgc:55578}, Mak (male germ cell-associated kinase) [NCBI Gene 17152] {aka A930010O05Rik}, Mks1 (MKS transition zone complex subunit 1) [NCBI Gene 380718] {aka B8d3, avc6}, Tbc1d32 (TBC1 domain family, member 32) [NCBI Gene 544696] {aka Bromi, C6orf170, D630037F22Rik, b2b2284Clo} - **Diseases:** AR (MESH:D020821), Ciliary Defects (MESH:D002925), Degeneration (MESH:D009410), LCA2 (MESH:C536601), renal abnormalities (MESH:D007674), Inherited Retinal Diseases (MESH:D012164), BBS (MESH:D020788), -linked (MESH:C536424), IRD (MESH:D052919), abnormalities of the retina, kidneys, skeleton, and liver (MESH:D000130), polydactyly (MESH:D017689), non-syndromic RP (MESH:C537612), postaxial polydactyly (MESH:C562429), chronic (MESH:D002908), cerebellar ataxia (MESH:D002524), photoreceptor death (MESH:D003643), intellectual disability (MESH:D008607), LCA (MESH:D057130), retinal dystrophy (MESH:D058499), Retinal defects (MESH:D012173), cytotoxicity (MESH:D064420), XL (MESH:D000080345), inherited retinal degeneration (MESH:D012162), multiorgan developmental defects (MESH:D000094602), JS (MESH:C536293), obesity (MESH:D009765), RP (MESH:D012174), rod impairment (MESH:D017696), vestibular dysfunction (MESH:D015837), nystagmus (MESH:D009759), ocular structural anomalies (MESH:C536503), sensorineural hearing loss (MESH:D006319), Defects in ciliary genes (MESH:D030342), hearing loss (MESH:D034381), hypogonadism (MESH:D007006), X-linked RP (MESH:C567523), cerebellar malformation (MESH:D002526), blinding (MESH:D001766), cone degeneration (MESH:C566719), autosomal recessive ciliopathy (MESH:D000072661), Digenic (MESH:D003398), Inflammation (MESH:D007249), neurodegeneration (MESH:D019636), metabolic disturbance (MESH:D024821), defects (MESH:D000013), loss (MESH:D016388), vision loss (MESH:D014786), DD (MESH:C536170), night blindness (MESH:D009755), LCA type 10 (MESH:C565720), USH (MESH:D052245), CRD (MESH:D000071700), deafness (MESH:D003638), AD (MESH:C566739), XLR (MESH:D040181), renal developmental anomalies or functional impairment (MESH:C535986) - **Chemicals:** lipid (MESH:D008055), EDIT-101 (-), lipofuscin (MESH:D008062), fluorocarbon (MESH:D005466), emixustat (MESH:C000592692), vitamin A (MESH:D014801), chitosan (MESH:D048271), oxygen (MESH:D010100), Mtz (MESH:D008795) - **Species:** Danio rerio (leopard danio, species) [taxon 7955], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Adeno-associated virus (species) [taxon 272636], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** C150S ## Figures 3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12966366/full.md --- Source: https://tomesphere.com/paper/PMC12966366