Cysteine cathepsin (CTS (for family), individual enzymes as CTSB, CTSC, CTSK, etc.)

Cysteine cathepsins are a family of proteolytic enzymes (cysteine proteases) mainly found within lysosomes but also active in other cellular compartments and extracellularly[1][3][4]. They are responsible for protein degradation, processing antigens for immune presentation, and extracellular matrix remodeling, among other roles. The human genome encodes 11 cysteine cathepsins (B, C, F, H, K, L, O, S, V/L2, W, Z/X), most of which are synthesized as inactive proenzymes that require proteolytic processing to become active[1][3][4]. Dysregulation or overexpression of cysteine cathepsins is implicated in a variety of diseases including cancer, neurodegeneration, inflammation, infections, and metabolic bone disorders[3][6]. Their characteristic mechanism involves a catalytic cysteine residue in the active site, making them targets for small-molecule inhibitors, both for research purposes and as potential therapies[2][5][6]. Selectivity among family member targeting has been challenging due to structural similarities, but certain inhibitors (e.g., odanacatib) have entered advanced clinical development primarily for osteoporosis, although safety concerns have limited therapeutic success[6]. The cathepsin family’s key biological and disease-associated activities, extensive research on inhibition, and broad tissue distribution make them recognized and validated molecular drug targets[1][2][3][6].

Other names

Papain-like cysteine proteaseCathepsin BCathepsin CCathepsin FCathepsin HCathepsin KCathepsin LCathepsin OCathepsin SCathepsin VCathepsin WCathepsin X/ZCathepsin P (mouse)Cathepsin L2 (V)

Inhibition of catalytic cysteine residue to block protease activity; Allosteric inhibition; Reversible and irreversible binding to active site; Competitive and non-competitive inhibition; Modulation of enzyme activity to affect extracellular matrix degradation and antigen presentation