CRADD (CARD and death domain containing adaptor protein) is a dual-domain adaptor protein that plays crucial roles in apoptosis regulation and cortical development. The protein contains an N-terminal caspase recruitment domain (CARD) and a C-terminal death domain, enabling interactions with multiple apoptotic signaling molecules 1. CRADD's primary function involves forming the PIDDosome complex with PIDD1 and caspase-2, which activates caspase-2 and triggers apoptosis 2. Additionally, CRADD recruits caspase-2 to TNFR-1 signaling complexes through interactions with RIPK1 and TRADD, participating in tumor necrosis factor-mediated pathways 1. Beyond apoptosis, CRADD functions as an anti-inflammatory regulator in endothelial cells by negatively controlling BCL10-mediated responses to proinflammatory stimuli, thereby maintaining vascular barrier function 3. Clinically, CRADD mutations cause intellectual developmental disorder with variant lissencephaly, characterized by megalencephaly, pachygyria, and seizures 4 5. These mutations impair CRADD's ability to activate caspase-2, resulting in reduced neuronal apoptosis during brain development 4. The phenotype suggests that proper CRADD/caspase-2 signaling is essential for normal cortical gyration and cognitive development, with defective programmed cell death contributing to cortical malformations.