TRIB2 (tribbles pseudokinase 2) is a scaffolding pseudokinase that regulates protein stability through the ubiquitin-proteasome system. TRIB2 lacks traditional kinase activity but functions as an adaptor protein that facilitates proteasomal degradation of target proteins by linking substrates to E3 ubiquitin ligases 1. Key substrates include the transcription factor C/EBPα and the cell cycle regulator CDC25C, with TRIB2 promoting CDC25C ubiquitination and degradation through its kinase-like domain 2. TRIB2 expression oscillates during the cell cycle and regulates cellular proliferation 2. The protein plays critical roles in immune cell homeostasis, particularly in naive T cells where it suppresses AKT activation to maintain quiescence, with higher expression in CD4+ versus CD8+ T cells contributing to their differential aging resistance 3. TRIB2 also functions as a scaffold linking the E3 ligase Cop1 to C/EBPδ, leading to C/EBPδ polyubiquitination and degradation, which affects macrophage infiltration in cancer 4. Clinically, TRIB2 is implicated in various cancers including leukemia and serves as a potential biomarker 56. Additionally, TRIB2 influences stem cell fate decisions and is associated with cardiovascular disease through regulation of adipose tissue 7.