The protein coded by the X‐adrenoleukodystrophy gene is a peroxisomal integral membrane protein

Abstract

The gene for adrenoleukodystrophy (X‐ALD), a peroxisomal disease characterized by excessive accumulation of very long‐chain (VLC) fatty acids (> C_22;0), has recently been identified by positional cloning, and it is predicted to encode a protein (ALD‐P) of 745 amino acids [(1993) Nature 361, 726]. Using Western blot analysis of subcellular organelles purified by isopycnic density gradient centrifugation from X‐ALD and control fibroblasts, we show that the monoclonal antibodies directed against ALD‐P cross‐react with a 75 kDa protein in intact peroxisomes and that ALD‐P is an integral component of the peroxisomal membrane. Moreover, no signal for ALD‐P was detected in peroxisomes from X‐ALD patients with deletion of the ALD gene.