Agrin is a heparan sulfate proteoglycan involved in the development of the neuromuscular junction during embryogenesis. In addition to this well-characterized function, agrin may have additional functions in other tissues and during other stages in development. In this study we present the cDNA sequence of human agrin, and demonstrate a high agrin content in adult basement membranes. The N-terminal domain of human agrin is highly similar to that of chick agrin, suggesting a similar function in laminin binding. The presence of three SGXG sequences supports serine-linked glycosylation of the core protein, two sites being particularly favorable for heparan sulfate attachment. Comparison of levels of agrin mRNA in fetal and adult human tissues showed a remarkable upregulation in adult kidney and lung. In both tissues truncated agrin transcripts were detected, lacking the region that encodes the laminin-binding domain. The high transcription levels in lung and kidney corresponded with the accumulation of agrin in the alveolar and glomerular basement membranes, suggesting a filtration-associated function. These data provide new directions for investigating the role of agrin in its different physiological environments, including the basement membranes of the neuromuscular junction, kidney and lung.Keywords : agrin; heparan sulfate proteoglycan ; glomerular basement membrane ; alveolar basement membrane ; neuromuscular junction.Agrin is a heparan sulfate proteoglycan (HSPG) of basement · glycoprotein complex [20]. Thus, agrin may anchor the BM to the cytoskeleton and be involved in signal transduction. Furthermembranes (BM). It induces aggregation of acetylcholine receptors at the neuromuscular junction (NMJ) [1, 2]. The primary more, agrin was identified recently as a major HSPG of the glomerular BM [21]. Here it could participate in the charge-selecstructures of the protein from electric ray, rat, mouse and chick have been reported [3Ϫ6]. The agrin gene was shown to encode tive ultrafiltration process. Agrin could be involved in the storage, activation, inhibition or presentation of various growth multiple isoforms through alternative splicing at three sites, designated x, y and z. These splice variants differ greatly in func-factors, and modulate their effect in a tissue-dependent manner.The human agrin gene was mapped previously to chromotion [6Ϫ9]. During the formation of the NMJ (the contact site of a motoneuron and a skeletal muscle cell), agrin isoforms ex-some 1 [5], but the cDNA structure is unknown. To obtain cDNA clones encoding full-length agrin, we used expressed-sepressed by motoneurons induce the clustering of acetylcholine receptors within the post-synaptic membrane. Isoforms ex-quence-tag information from public databases [18,22]. Here, we report the cDNA sequence of human agrin, and provide data pressed by the muscle cell do not have a clustering activity [6, 10Ϫ12]. Agrin-related proteins are also expressed in non-neural concerning its distribution in human tissues. tissues, suggesting functions in ...