Papain-like cysteine proteases are widely expressed enzymes that mostly regulate protein turnover in the acidic conditions of lysosomes. However, in the last twenty years, these proteases have been evidenced to exert specific functions within different organelles as well as outside the cell. The most studied proteases of this family are human cysteine cathepsins involved both in physiological and pathological processes. The specificity of each protease to its substrates is mostly defined by the structure of the binding cleft. Different patterns of amino acid motif in this area determine the interaction between the protease and the ligands. Moreover, this specificity can be altered under the specific media conditions and in case other proteins are present. Understanding how this network works would allow researchers to design the diagnostic selective probes and therapeutic inhibitors. Moreover, this knowledge might serve as a key for redesigning and de novo engineering of the proteases for a wide range of applications.

木瓜蛋白酶样半胱氨酸蛋白酶是广泛表达的酶，主要调节溶酶体酸性条件下的蛋白质周转。然而，在过去的二十年中，这些蛋白酶已被证明在不同细胞器内以及细胞外发挥特定功能。该家族中研究最多的蛋白酶是参与生理和病理过程的人半胱氨酸组织蛋白酶。每种蛋白酶对其底物的特异性主要由结合裂隙的结构决定。该区域中氨基酸基序的不同模式决定了蛋白酶与配体之间的相互作用。此外，这种特异性可以在特定的培养基条件下以及在存在其他蛋白质的情况下发生改变。了解该网络的工作原理将使研究人员能够设计诊断选择性探针和治疗抑制剂。此外，这些知识可以作为重新设计和用于广泛应用的蛋白酶的从头工程。