ASB6 (ankyrin repeat and SOCS box containing 6) is a substrate-recognition component of the CUL5-ASB6 E3 ubiquitin-protein ligase complex that mediates ubiquitination and proteasomal degradation of target proteins 1. The complex promotes K48-linked ubiquitination of key regulatory proteins including p62/SQSTM1 and INSIG1 12, thereby regulating cell proliferation and autophagy. ASB6 overexpression suppresses cell proliferation by reducing p62 levels and impairing autophagy in multiple cell types 1. In cancer contexts, ASB6 demonstrates dual regulatory roles: it can be targeted for degradation by RNF41-mediated ubiquitination in colorectal cancer, where elevated ASB6 promotes stemness and metastasis 3, and it enhances oral squamous cell carcinoma malignancy by attenuating endoplasmic reticulum stress and promoting cancer stem-like cell properties 4. ASB6 upregulation is associated with betel quid-induced oral carcinogenesis and correlates with poor prognosis in oral, pregnancy-associated breast, and colorectal cancers 56. Elevated ASB6 expression represents a prognostic marker for multiple cancer types and potential therapeutic target for cancer treatment.