Calpain5 (CAPN5) is a nonclassical calpain in that it lacks a pentaEF hand domain. Although widely expressed dominantly inherited mutations of CAPN5 display phenotypes primarily localized to the eye. These experiments aimed to identify proteins from the neuroblastoma cell line SH-SY5Y that may interact with the catalytic core domain of CAPN5 (phe2-leu348) and to complement co-immunoprecipitation studies using SH-SY5Y cell overexpressing full length CAPN5. Given that domains are independent folding units within the intact protein and interacting surfaces are in general localized some valid interacting proteins are expected to be captured. It is also clear that some interacting partners may be lost due to a decreased number of, or affinity of, interactions..