SIAH1 (siah E3 ubiquitin protein ligase 1) is an E3 ubiquitin ligase that plays crucial roles in protein degradation and cellular homeostasis. The protein mediates ubiquitination and proteasomal degradation of numerous substrates by accepting ubiquitin from E2 enzymes and transferring it to target proteins 1. SIAH1 functions through direct substrate binding or as part of larger E3 complexes, targeting proteins involved in transcription regulation, cell signaling, and structural functions 1. The enzyme operates through a novel mechanism where small molecules can induce target protein polymerization, leading to sequestration and subsequent degradation, as demonstrated with BCL6 degradation 1. SIAH1 is involved in critical cellular processes including apoptosis, Wnt signaling through AXIN2 regulation 2, and hypoxia response via HIF-1α pathway modulation 3. In disease contexts, SIAH1 exhibits dual roles: promoting glioma cell migration and invasion under hypoxic conditions 3, facilitating hepatocellular carcinoma survival through mitophagy regulation 4, and mediating PPARγ degradation in bladder cancer 5. The protein's dysregulation contributes to various pathological conditions, making it a potential therapeutic target for cancer treatment 6. SIAH1's complex regulatory network and diverse substrate specificity highlight its importance in maintaining cellular protein homeostasis.