Testis-specific Y-encoded-like protein 1 (TSPYL1)

Testis-specific Y-encoded-like protein 1 (TSPYL1) is a chromatin-associated regulatory protein encoded by the TSPYL1 gene on chromosome 6. It contains a nucleosome assembly protein (NAP) domain, involved in controlling chromatin structure and transcription. TSPYL1 is expressed in the brain, testes, and other tissues and participates in key developmental processes, notably male reproductive tract and brainstem formation. Loss-of-function mutations in TSPYL1 cause SIDDT, a lethal syndrome of abnormal organ development, particularly in the Amish community. TSPYL1 functions as a negative regulator of Wnt/β-catenin signaling—affecting cholesterol metabolism through modulation of cytochrome P450 enzymes such as CYP1B1 and CYP7A1. TSPYL1 also represses TGFBR1 transcription by partnering with FOXA1 and EZH2, impacting cellular sensitivity to TGFβ signaling. There is emerging interest as a regulatory node in metabolic and cell signaling pathways, but no approved drugs or established biomarkers currently exist for clinical targeting of TSPYL1.

Other names

TSPYL1TSPYLTSPY-like protein 1TSPY like 1testis-specific Y-encoded-like protein 1

Not applicable; no drugs currently target TSPYL1. Mechanistically, TSPYL1 regulates transcription by modulating chromatin, nucleosome assembly, and key signaling pathways (Wnt/β-catenin, TGFβ).