BRAP (BRCA1-associated protein) is a cytoplasmic E3 ubiquitin ligase that negatively regulates mitogen-activated protein kinase (MAPK) signaling by limiting Raf/MEK complex formation through inactivation of the KSR1 scaffold protein [UniProt]. Upon Ras activation, BRAP undergoes auto-polyubiquitination, releasing its inhibition of Raf/MEK signaling [UniProt]. Beyond MAPK regulation, BRAP functions as a Ras-responsive ubiquitin ligase and may participate in nuclear transport regulation [UniProt]. BRAP's broader physiological roles extend beyond canonical MAPK signaling. In hepatic tissue, BRAP modulates the Hippo pathway by regulating MST2 kinase, controlling hepatocyte proliferation, morphology, and liver lipid accumulation during obesity 1. In kidney injury models, BRAP regulates SIRT2 protein stability through interactions with the E3 ubiquitin ligase HRD1, affecting tubular cell apoptosis and necroptosis during cisplatin-induced acute kidney injury 2. BRAP expression is downregulated in diseased kidneys and is transcriptionally suppressed by NF-κB P65 under stress conditions 2. Given BRAP's association with BRCA1 and emerging roles in metabolic and cardiovascular disease pathways 3, understanding BRAP's mechanistic contributions beyond cancer biology may illuminate therapeutic targets in multiple disease contexts.