NLRC4 inflammasome is activated by a few gram-negative bacteria that express type III or type IV secretion systems. Examples of gram-negative bacteria that activate NLRC4 inflammasome are Pseudomonas aeruginosa, Shigella flexneri, legionella pneumophila, and Salmonella typhimurium.

Autoinflammation With Infantile Enterocolitis and Familial Cold Autoinflammatory Syndrome are two common diseases associated with NLRC4 activation.