The acid-labile subunit (ALS) of the insulin-like growth factor (IGF) binding protein (IGFBP) complex, encoded in humans by IGFALS, has a vital role in regulating the endocrine transport and bioavailability of IGF-1 and IGF-2. Accordingly, ALS has a considerable influence on postnatal growth and metabolism. ALS is a leucine-rich glycoprotein that forms high-affinity ternary complexes with IGFBP-3 or IGFBP-5 when they are occupied by either IGF-1 or IGF-2. These complexes constitute a stable reservoir of circulating IGFs, blocking the potentially hypoglycaemic activity of unbound IGFs. ALS is primarily synthesized by hepatocytes and its expression is lower in non-hepatic tissues. ALS synthesis is strongly induced by growth hormone and suppressed by IL-1β, thus potentially serving as a marker of growth hormone secretion and/or activity and of inflammation. IGFALS mutations in humans and Igfals deletion in mice cause modest growth retardation and pubertal delay, accompanied by decreased osteogenesis and enhanced adipogenesis. In hepatocellular carcinoma, IGFALS is described as a tumour suppressor; however, its contribution to other cancers is not well delineated. This Review addresses the endocrine physiology and pathology of ALS, discusses the latest cell and proteomic studies that suggest emerging cellular roles for ALS and outlines its involvement in other disease states.

胰岛素样生长因子 (IGF) 结合蛋白 (IGFBP) 复合物的酸不稳定亚基 (ALS) 在人体中由IGFALS编码，在调节 IGF-1 和 IGF-2 的内分泌运输和生物利用度方面发挥着至关重要的作用。因此，ALS对产后生长和代谢有相当大的影响。 ALS 是一种富含亮氨酸的糖蛋白，当 IGFBP-3 或 IGFBP-5 被 IGF-1 或 IGF-2 占据时，会与 IGFBP-3 或 IGFBP-5 形成高亲和力的三元复合物。这些复合物构成了循环 IGF 的稳定库，阻断了未结合的 IGF 的潜在降血糖活性。 ALS主要由肝细胞合成，在非肝组织中表达较低。 ALS 合成受到生长激素的强烈诱导并受到 IL-1β 的抑制，因此有可能作为生长激素分泌和/或活性以及炎症的标志物。人类的IGFALS突变和小鼠的Igfals缺失会导致适度的生长迟缓和青春期延迟，并伴有骨生成减少和脂肪生成增强。在肝细胞癌中，IGFALS被描述为肿瘤抑制因子；然而，它对其他癌症的影响尚不清楚。这篇综述讨论了 ALS 的内分泌生理学和病理学，讨论了最新的细胞和蛋白质组学研究，这些研究表明 ALS 的新兴细胞作用，并概述了其与其他疾病状态的关系。