NALP6 belongs to the NLRP family of which function as innate sensors of endogenous and exogenous stress and damage-associated molecular patterns (DAMPs). NLRPs are vital components of the inflammasome which is the cytoplasmic multiprotein complex that coordinates inflammation and cell homeostasis in various type of cells/tissues. NALP6 is one of the newest NLR protein family members and is highly expressed in intestinal epithelium and granulocytes, and to a relatively lower level in T-cells. NALP6 behaves as an arginine-vasopressin V2 receptor and has been suggested to contribute to AVP-mediated regulation of renal salt-water balance, glucose and lipid metabolism, apoptosis, and the cell cycle.
NALP6 has been shown to actively participate in inflammasome signaling and to play a critical role in defense against infection, auto-inflammation, and tumorigenesis. The function of NALP6 in innate immunity, as a negative regulator of inflammatory signaling, and clearing bacterial pathogens was published in Nature by Anand’s group at St. Jude Children’s Research Hospital (1). Furthermore, a comprehensive review by the same group discusses recent data and studies on NALP6 key functions in infection and inflammation (2). They share insights on how NALP6 inhibition of NF-kB and MAP-kinase dependent signaling enables the maintenance of gut microbiota composition. Another recent related review from Chen focuses on the role of NALP6 and NLRP12 as important players in on intestinal homeostasis (3). Insights from new studies are helping to model current ideas of how the NLRP family protects against colitis and tumorigenesis.
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