Procaspase‑9 is processed in an ATP‑dependent manner following association with APAF1 and cytochrome c (CYCS) within the apoptosome complex (Li P et al. 1997). However, caspase‑9 (CASP9) has an unusually active zymogen that does not require proteolytic processing (Stennicke HR et al. 1999). Though dispensable for catalytic activity, CASP9 processing was suggested to serve as a "molecular timer" that can limit the proteolytic activity of this complex through displacement of bound caspase‑9 molecules (Malladi S et al. 2009). In addition, this cleavage exposes a neo‑epitope comprising the NH2‑terminal four amino acids (ATPF) of the small p12 subunit of CASP9 that has been shown to be both necessary and sufficient for binding to the baculovirus IAP repeat 3 (BIR3) domain of XIAP, leading to inhibition of CASP9 activity (Srinivasula SM et al. 2001; Shiozaki EN et al. 2003).