Yeast two-hybrid screening of mouse cDNA libraries was performed to identify proteins interacting with selenocysteine lyase (SCL), which decomposes L-selenocysteine. Several proteins related to spermatogenesis, protein synthesis, and cell viability/apoptosis were identified as potential interactors. Major urinary proteins 1 and 2 interacted with SCL and inhibited its activity. Coimmunoprecipitation revealed interactions between SCL and each of two selenophosphate synthetase isozymes.