FAF1 (Fas Associated Factor 1) is a ubiquitin-binding protein with diverse cellular functions beyond its initial identification in Fas-mediated apoptosis. (a) Primary function: FAF1 serves as a regulatory protein in protein quality control, apoptosis, and developmental processes 1. It is required for DNA replication fork progression by targeting the replication licensing factor CDT1 for degradation and functions as a component of the VCP-NPL4-UFD1 complex involved in aggresome clearance 2. (b) Mechanism: FAF1 operates through multiple pathways including NF-κB signaling regulation, ubiquitin-proteasome system interactions, and protein degradation processes 13. It plays a crucial role in aggresome disassembly by working with p97/VCP to remove ubiquitylated proteins, enabling subsequent autophagy 2. (c) Disease relevance: FAF1 disruption is associated with cleft palate through its role in cranial neural crest cell differentiation 4. Its downregulation contributes to gastric carcinogenesis in H. pylori infections and affects mitochondrial dysfunction pathways 5. (d) Clinical significance: FAF1 expression levels correlate with prognosis in various cancers, with high expression indicating poor outcomes in non-small-cell lung cancer 6, establishing it as both a developmental regulator and potential tumor suppressor.