receptors such as NOD-like receptors containing a pyrin domain (NRLPs) and AIM2-like receptors (ALRs). ASC ASC is an adaptor protein and is part of apoptosis, pro-caspase 1 recruitment and activation, as well as NF-κB transcription factor activation. ASC contains only two domains: the PYD domain at the N-terminus and a CARD (caspase recruitment domain) at the C-terminus. Pyrin domain interactions between ASC leads to oligomerization forming puncta or "specks" that become visible microscopically. The CARD domain recruits pro-caspase-1 which undergoes proximity induced autocleavage to form the active caspase-1 which in turn triggers maturation of IL-1β and IL-18. NLRPs NOD-like receptors exist in an inactive form until a conformational change is induced by their ligand. Some NLRs such as NLRP1 and NLRP2 have a straightforward mechanism by which the receptor binds to a PAMP triggering its activation, oligomerization and PYD-PYD ASC recruitment. In contrast, NLRP3 (also known as cryopyrin) is the most well-studied NLR with a pyrin domain and has several diverse agonists. Proposed methods of its activation are more nuanced with intermediate effectors instead of a direct ligand-receptor interaction. An efflux of ATP due to tissue damage leading to an increase in Ca2+, mitochondrial reactive oxygen species production due to cellular stress and lysosomal rupture releasing excess H+ have all been proposed to inhibit different cofactors that normally inactivate NLRP3. ALRs Absent in melanoma 2-like receptors function as recognition of foreign double stranded DNA. Two ALRs with pyrin domains, AIM2 and IFI16, assemble inflammasomes; AIM2 in the cytosol and IFI16 moves between the nucleus and cytosol functioning as a nuclear pathogen sensor. Unlike NLRPs which function in cytosolic PAMP and DAMP recognition, ALRs mainly act within the nucleus oligomerizing along the DNA staircase. POPs Pyrin-only proteins are unlike other PYD-containing proteins which contain a pyrin domain with one or more other domains. Different POPs have electrostatic and structural similarities to the specific pyrin domains they regulate. Most are encoded near the same genes as the pyrin-containing proteins they inhibit; POP1 and POP2 are postulated to have arisen by exon duplication. Since most inflammasomes are formed by aggregation due to PYD-PYD interactions, POPs instead bind to PYD domains preventing polymerization and therefore regulating and/or resolving inflammation response. References Protein domains