# Current Research Progress on ABHD5 in Cancers

## TL;DR

ABHD5, a protein involved in lipid metabolism, has complex and context-dependent roles in cancer, acting as both a tumor suppressor and promoter depending on the cancer type.

## Contribution

This review synthesizes experimental and clinical evidence to clarify ABHD5's multifaceted roles in cancer and its potential as a diagnostic and therapeutic target.

## Key findings

- ABHD5 can suppress tumor growth in lung, liver, and renal cell carcinomas.
- In endometrial cancer, ABHD5 promotes malignant progression.
- ABHD5 interacts with AMPK/mTOR, AKT, and NF-κB pathways to influence cancer cell behavior.

## Abstract

ABHD5 is a key regulator of lipid metabolism, with context-dependent roles in cancer. It interacts with signaling pathways like AMPK/mTOR, AKT, and NF-κB, exerting either tumor-suppressive or oncogenic effects based on the tumor’s ecological and molecular context. This review synthesizes experimental and clinical evidence to clarify its multifaceted functions and explores its potential as a diagnostic marker and therapeutic target, emphasizing the need for precision strategies rather than blunt intervention.

Lipid metabolism sits at the heart of tumor initiation, progression, metastasis, and resistance to chemotherapy. Against this background, the regulation of lipid flux has emerged as a fertile ground for anticancer strategies. Chanarin–Dorfman syndrome (CDS), a rare genetic disorder marked by massive lipid droplet accumulation, offers compelling human evidence that α/β-hydrolase domain-containing protein 5 (ABHD5) plays a central role in lipid droplet mobilization through the ATGL axis. This clinical insight has, perhaps unexpectedly, pushed ABHD5 into the spotlight of cancer research. ABHD5 does not behave uniformly across malignancies. In many solid tumors—such as lung, liver, and renal cell carcinoma—it restrains tumor growth. Yet in other settings, notably endometrial cancer, it appears to fuel malignant progression. Colorectal and prostate cancers occupy a more ambiguous middle ground, where ABHD5 can tip the balance in either direction depending on context. Mechanistically, ABHD5 influences lipid homeostasis and cell fate by intersecting with signaling pathways including AMPK/mTOR, AKT, and NF-κB, thereby shaping proliferation, invasion, apoptosis, immune evasion, and drug responsiveness. This review brings together experimental and clinical evidence to map the diverse, sometimes contradictory roles of ABHD5 in cancer. By tracing its context-dependent functions and molecular circuits, we also explore its emerging value as a diagnostic marker and a therapeutic target—one that demands nuance rather than blunt intervention.