The invention provides caspase recruitment domain (CARD)-containing polypeptides and functional fragments thereof, encoding nucleic acid molecules, and specific antibodies. Also provided are screening methods for identifying CARD-associated polypeptides (CAPs), and for identifying agents that alter the association of a CARD-containing polypeptide with itself or with a CAP. Further provided are methods of altering a biochemical process modulated by a CARD-containing polypeptide, and methods of diagnosing a pathology characterized by an increased or decreased level of a CARD-containing polypeptide.