CARF (calcium-responsive transcription factor, also known as CDKN2AIP) is a multifunctional transcriptional regulator with primary roles in cellular stress response and metabolic homeostasis. As a calcium-responsive transcription factor, CARF acts as a transcriptional activator mediating neuron-selective induction of BDNF exon III transcription by binding calcium-response elements 1. Beyond calcium signaling, CARF functions as a molecular bridge between cellular senescence and proliferation through regulation of the p53-HDM2-p21 axis, stabilizing p53 and acting as a transcriptional repressor of HDM2 12. CARF overexpression induces premature senescence via p53-p21 and p16-pRB pathway upregulation, while CARF knockdown causes mitotic arrest and apoptosis 2. Recently, CARF has been implicated in metabolic regulation: fatty acid excess downregulates hepatic CARF expression, and CARF overexpression protects against nonalcoholic fatty liver disease by suppressing endoplasmic reticulum and oxidative stress while improving insulin sensitivity 3. Clinically, CARF expression is associated with lacunar stroke susceptibility through transcriptome-wide association 4. CARF also participates in cellular stress responses as a component of FMRP interaction networks regulating ribonucleoprotein stress granule formation and DNA damage response 5.