Ubiquilin-2 (UBQLN2)

Ubiquilin-2 (UBQLN2) is a ubiquitin-like protein that functions as an adaptor or shuttle, linking ubiquitinated proteins to the proteasome to facilitate their degradation and maintain protein quality control in cells. It has an N-terminal ubiquitin-like (UBL) domain, a C-terminal ubiquitin-associated (UBA) domain, and internal disordered regions including a unique proline-rich (PXX) domain. UBQLN2 is widely present in the nucleus and cytoplasm, forming puncta under stress conditions and self-assembling into dynamic liquid-like condensates. Mutations in UBQLN2, particularly in the PXX domain, cause familial forms of amyotrophic lateral sclerosis and frontotemporal dementia by promoting toxic protein aggregation and disrupting normal proteostasis[1][2][3][4]. UBQLN2 interacts with proteasomes, autophagic proteins, molecular chaperones, and ubiquitin ligases, and plays a central role in the clearance of misfolded and damaged proteins as well as in cellular responses to protein aggregation stress. UBQLN2 is not currently a direct therapeutic target, but is of interest in drug discovery for neurodegenerative disorders.

Other names

UBQLN2N4BP4PLIC2HRIHFB2157PLIC-2hPLIC-2Chap1Dsk2RIHFB2157LIC-2CHAP1/DSK2NEDD4 binding protein 4ALS15CHAP1DSK2protein linking IAP with cytoskeleton 2ubiquitin-like product Chap1/Dsk2

Not applicable for approved drugs as UBQLN2 is not yet a direct therapeutic target. Potential mechanisms (preclinical/experimental) would include modulation of proteasome/ubiquitin-proteasome pathway, protein aggregation prevention, or autophagy enhancement.