26S proteasome regulatory subunit 6A

PSMC3 (26S proteasome regulatory subunit 6A) is an AAA-ATPase component of the 26S proteasome complex that mediates ATP-dependent degradation of ubiquitinated proteins (UniProt: P17980). The protein belongs to the heterohexameric ring that unfolds target proteins for translocation into the proteolytic chamber, thereby maintaining cellular protein homeostasis and supporting processes including cell cycle progression, apoptosis, and DNA repair.

PSMC3 is widely expressed and functions in protein quality control across multiple cellular compartments. UniProt documents an association with autosomal recessive deafness, cataract, impaired intellectual development, and polyneuropathy (DCIDP, MIM 619354), indicating the functional importance of proteasomal degradation during development (UniProt: P17980).

In Alzheimer's Disease, PSMC3 is significantly downregulated in post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics, mean log2FC −0.31). This reduction in a core proteasomal subunit may reflect impaired protein degradation capacity in AD pathology, potentially contributing to accumulation of misfolded proteins characteristic of neurodegeneration.