Intramembrane proteases catalyze the unusual cleavage of peptide bonds in the plane of biological membranes. They are categorized according to their active site. The GxGD aspartyl proteases comprise presenilin, the signal peptide peptidase (SPP), and SPP-like (SPPL) proteases. Here we focus on the functionally related SPP and SPPL proteases, and review the current understanding of their substrate specificity and summarize known physiological functions in mammalian cells. We discuss how on the one hand regulated intramembrane proteolysis generates signaling molecules, and on the other hand how processes such as endoplasmic reticulum-associated degradation controls the quantity and activity of central regulators. While the enzymatic core of GxGD intramembrane proteases is conserved, association with regulatory factors and substrate adaptors may have tailored enzymes for various specific functions.

膜内蛋白酶催化生物膜平面内肽键的异常裂解。它们是根据其活动站点进行分类的。GxGD天冬氨酰蛋白酶包括早老蛋白，信号肽肽酶（SPP）和SPP样（SPPL）蛋白酶。在这里，我们专注于功能相关的SPP和SPPL蛋白酶，并综述了它们对底物特异性的当前理解，并总结了哺乳动物细胞中已知的生理功能。我们讨论一方面调节膜内蛋白水解如何产生信号分子，另一方面讨论诸如内质网相关降解的过程如何控制中央调节剂的数量和活性。虽然GxGD膜内蛋白酶的酶核心是保守的，