One type of inherited colon cancer predisposition, familial adenomatous polyposis (FAP), results from mutations in a single gene known as adenomatous polyposis coli (APC). Recent studies from our laboratory indicate that APC may promote colonocyte differentiation by stimulating the production of retinoic acid. Retinoic acid is a lipid mediator with important roles in controlling cell patterning, fate, and differentiation. Central to the ability of a cell to respond to retinoic acid is the requirement of first converting dietary retinol (vitamin A) into retinoic acid, a process that occurs via two enzymatic steps. The first step of this process converts retinol into retinal and is mediated by alcohol dehydrogenases (ADH) and short chain dehydrogenases (SDR). The second step involves conversion of retinal into retinoic acid via aldehyde dehydrogenases (ALDH). Given the required conversion of vitamin A, retinoic acid production is limited to cells harboring the necessary biosynthetic enzymes. We have demonstrated that loss of retinoic acid production is an early event following mutation of APC and that this contributes to the mis-fating of intestinal epithelial cells.