# TSPY-like 2, Beyond the Histone Chaperone Role

## TL;DR

This review explores the diverse roles of TSPYL2, a histone chaperone, beyond chromatin assembly, including its links to diseases and sex-related functions.

## Contribution

The paper highlights new and unexpected roles of TSPYL2, such as sex-related activity and disease associations, beyond its known histone chaperone function.

## Key findings

- TSPYL2 regulates transcription, cell-cycle progression, and DNA-damage response independently of chromatin assembly.
- Defects in TSPYL2 are linked to cancer and neurodevelopmental abnormalities.
- TSPYL2 exhibits sex-related activity, suggesting a broader functional role.

## Abstract

Chromatin is a dynamic cellular structure basically constituted by nucleosomes, which consist of a DNA sequence wrapped around an octameric histones core. Histone synthesis and transport, nucleosome formation and proper chromatin assembly is an ordered and stepwise process guided by histone chaperones. Several families of histone chaperones have been identified and one of them is the nucleosome assembly protein (NAP) superfamily. Members of this family have been involved not only in chromatin constitution and regulation but also in several other cellular processes, such as nucleocytoplasmic shuttling, DNA replication, transcription and cell-cycle regulation. Testis specific protein Y-like 2 (TSPYL2) is a peculiar member of the NAP superfamily of histone chaperone. This protein has been initially isolated as a nuclear antigen in patients affected by discoid lupus erythematosus and as a TGF-β target. Its ability to bind histones has been demonstrated. In addition, TSPYL2 has been reported to regulate transcription, cell-cycle progression and the DNA-damage response, independently of its role in chromatin organization. In accordance with its multiple functions, defects in TSPYL2 have been associated with different diseases, mainly cancer and neurodevelopmental abnormalities. In this review we summarize and discuss the multiple cellular functions of TSPYL2, pointing out new and unexpected aspects like a sex-related activity and their relationship with different diseases.