Cysteine-rich with EGF-like domain protein 1 (CRELD1) is an ~50kD transmembrane glycoprotein that contains a 333 amino acid (aa) extracellular domain (ECD), two tandem transmembrane segments, and a second ECD of 15aa (1). Alternative splicing of human CRELD1 generates an additional isoform with a substitution that encompasses the transmembrane segments and the C-terminal ECD (1). CRELD1 is widely expressed during development and in the adult (1). It interacts with Reticulon 3/RTN3 and inhibits the pro-apoptotic activity of RTN3 (2). CRELD1 also associates with Adrenergic alpha1 receptors in the prostate and limits their expression (3). Missense mutations of human CRELD1 are associated with susceptibility to atrioventricular septal defects in the heart (4).