Cysteine protease that plays essential roles in programmed cell death, development and innate immunity (PubMed:11953316). Acts as a non-canonical executioner caspase during apoptosis: localizes in the nucleus and cleaves the nuclear structural protein lamin-A/LMNA thereby inducing nuclear shrinkage and fragmentation (PubMed:11953316). Lamin-A/LMNA cleavage is required for chromatin condensation and nuclear disassembly during apoptotic execution (PubMed:11953316). Plays an essential role in defense against viruses by acting as a central mediator of the ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis), independently of its cysteine protease activity. PANoptosis is a unique inflammatory programmed cell death, which provides a molecular scaffold that allows the interactions and activation of machinery required for inflammasome/pyroptosis, apoptosis and necroptosis (By similarity). Strict requirement for Asp at position P1 and has a preferred cleavage sequence of Val-Glu-His-Asp-|-. During activation, the N-terminal prodomain is removed by cleavage (By similarity). Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit (By similarity). The two large and two small subunits then assemble to form the active CASP6 complex (By similarity). Intramolecular cleavage at Asp-191 is a prerequisite for CASP6 self-activation (By similarity). Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit. Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit. Widely expressed. The N-terminal disordered prodomain is required to prevent self-activation. The Tri-arginine exosite is required to recruit substrates for hydrolysis. Undergoes helix-strand structural transitions upon substrate-binding: the 130's region interconverts between an inactive helical state and the canonically active strand state. Other caspases rest constitutively in the strand conformation before and after substrate-binding. Belongs to the peptidase C14A family.