UBAC2 (ubiquitin-associated domain containing 2) functions primarily as a selective autophagy receptor for endoplasmic reticulum (ER) degradation and a negative regulator of inflammatory responses. UBAC2 contains a canonical LC3-interacting region (LIR) that binds to autophagosomal GABARAP, facilitating selective ER-phagy 1. Upon ER stress or autophagy activation, the kinase MARK2 phosphorylates UBAC2 at serine 223, promoting its dimerization and enhancing interaction with GABARAP 1. This ER-phagy activity restrains inflammatory responses and acute ulcerative colitis in mice, suggesting UBAC2 directs ER degradation through a MARK2-UBAC2 axis 1. Additionally, UBAC2 participates in canonical Wnt signaling inhibition by promoting ubiquitin-mediated degradation of β-catenin and Wnt receptors, though details of this mechanism require further investigation. Dysregulation of UBAC2 is clinically relevant; increased UBAC2 expression promotes bladder cancer proliferation through the BCRC-3/miRNA-182-5p/p27 axis 2, while UBAC2 genetic polymorphisms are associated with susceptibility to Behçet's disease 3, noise-induced hearing loss 4, and ocular/CNS manifestations of Behçet's disease 5. These findings establish UBAC2 as a multifunctional protein linking ER homeostasis, autophagy, and immune regulation.