STUB1 encodes an E3 ubiquitin ligase that plays crucial roles in protein quality control and cellular homeostasis. The protein functions as a chaperone-dependent E3 ubiquitin ligase that targets misfolded proteins for proteasomal degradation, working in conjunction with heat shock proteins including Hsp70 and Hsp90 1. STUB1 regulates multiple cellular processes through selective ubiquitination of key substrates. It controls autophagy by targeting phosphorylated TFEB for degradation, thereby modulating autophagy-lysosome pathway activity 2. In cancer biology, STUB1 demonstrates both tumor suppressive and oncogenic functions depending on context. It promotes ferroptosis in gastrointestinal stromal tumors by mediating GPX4 ubiquitination, sensitizing cells to imatinib treatment 3, and suppresses paclitaxel resistance in ovarian cancer through HOXB3 ubiquitination 4. However, STUB1 can also promote cholangiocarcinoma progression by facilitating K63-linked ubiquitination of UHRF1, which maintains DNA hypermethylation 5. In immune regulation, STUB1 forms a complex with CHIC2 to negatively regulate CD8+ T cell anti-tumor responses by controlling cytokine receptor expression 6. Disease associations include spinocerebellar ataxia 48, highlighting its importance in neurological function 7. These diverse functions establish STUB1 as a critical regulator of protein homeostasis with significant therapeutic implications.