RIPK1 is a serine-threonine kinase functioning as a critical regulator of cell death and inflammation through both kinase-dependent and kinase-independent mechanisms 1. As a scaffold protein, RIPK1 is recruited to the TNF receptor signaling complex where it promotes cell survival via NF-κB activation 2. However, RIPK1 kinase activity orchestrates assembly of death-inducing complexes: complex IIa (RIPK1-FADD-CASP8) driving apoptosis and complex IIb (RIPK1-RIPK3-MLKL) driving necroptosis 2. RIPK1 normally inhibits RIPK3-mediated necroptosis through CASP8-dependent cleavage 3. Beyond cell death, RIPK1 promotes inflammatory signaling independent of cell death through ubiquitin-dependent mechanisms, particularly in response to ZBP1 activation 4. Recent discoveries reveal RIPK1 senses S-adenosylmethionine availability, linking metabolic status to cell death decisions 5, and undergoes palmitoylation licensing its kinase activity in inflammatory disease contexts 6. RIPK1 dysfunction contributes to neurodegeneration, ischemic injury, and metabolic disease 37. Clinically, RIPK1 inhibitors represent emerging therapeutics for autoimmune, inflammatory, and neurodegenerative conditions 1, while selective RIPK1 degradation enhances immunotherapy efficacy 8.