The small intestine contains three distinct proteins belonging to the intracellular lipid binding protein family: the liver-type fatty acid binding protein (L-FABP), the intestinal fatty acid binding protein (I-FABP) and the ileal lipid binding protein (ilbp). The function of these proteins in the small intestine has remained enigmatic. Targeted gene disruption studies may shed insights into the physiological importance of these proteins. In the case of I-FABP, this approach has demonstrated that the complete elimination of this protein in murine intestine does not compromise dietary fat absorption in vivo but is associated with the development of insulin resistance.