We have previously identified Serdin1/Lrrc10 as a cardiac-specific message that is expressed early in murine heart development and encodes a novel leucine-rich protein. A high degree of evolutionary conservation with respect to protein sequence, cardiac-specific expression, and cis-regulatory elements suggested that LRRC10 has an important and conserved function in cardiac development. Recently, the zebrafish lrrc10 knockdown models were described with a dramatic early defect in heart looping which supported the notion that Serdin1/Lrrc10 is likely to be essential for heart development in all vertebrates. To determine Lrrc10 function in mammalian cardiac development, we have disrupted the Lrrc10 gene in mice. We report here that, in striking contrast to the zebrafish lrrc10 knockdown, Lrrc10-null mice develop normally and exhibit no discernable phenotype.