MINDY3 is a K48-linked deubiquitinase that removes lysine-48-conjugated ubiquitin from proteins 1. As a member of the evolutionarily conserved MINDY family of deubiquitinating enzymes (DUBs), MINDY3 contains a structurally distinct catalytic domain with no homology to known DUBs and demonstrates high selectivity for cleaving K48-linked polyubiquitin chains, which typically signal protein degradation 1. The enzyme localizes to the nuclear membrane and nucleoplasm, suggesting roles in nuclear protein regulation [GO annotations]. MINDY3's involvement in proteostasis regulation implicates it in cellular processes requiring protein quality control. Evidence from a cigarette smoke-induced oxidative injury model identified MINDY3 within a five-gene sub-network (including MINDY2, CARD17, CARD18, and CASP1) associated with inflammation and oxidative stress responses 2. While MINDY3 has not been directly characterized for disease association, its structural relation to tumor-suppressor pathways on chromosome 10 and participation in stress-response networks suggests potential relevance to cancer and inflammatory diseases. The specific clinical significance of MINDY3 remains to be fully elucidated.