The death domain (DD) containing protein PIDD is a p53 target gene in an erythroleukemia cell line that undergoes G1 phase arrest and subsequent apoptosis after p53 expression. Independently, PIDD was also described as a DD-containing protein with unknown function. The N-terminal region of PIDD contains seven leucine-rich repeats (LRRs), a protein interaction motif found in various proteins with diverse functions, followed by two ZU-5 domains and a C-terminal DD. PIDD forms a complex with caspase-2 and the adaptor protein RAIDD. Increased PIDD expression results in spontaneous activation of caspase-2 and sensitization to apoptosis by genotoxic stimuli, via interaction with caspase-2 and CRADD/RAIDD. PIDD also promotes apoptosis downstream of p53 as component of the DNA damage/stress response pathway that connects p53/TP53 to apoptosis. PIDD has also been shown to interact with NEMO/IKBKG and RIP1 and enhance sumoylation and ubiquitination of NEMO/IKBKG, an important component for activation of the transcription factor NF-kappa-B.