TABLE 2.

Role of CatK beyond bone.

Tissues	Disease	Functions	References
Central nervous system	AIS	CatK is required for maintaining the BBB integrity while the absence of CatK activity might result in higher risk of rtPA-induced HT after cerebral ischemia.	Zhao et al., 2019
	CA	Inhibiting CatK could inhibit the excessive ECM degradation, and thus might be beneficial for preventing CA progression.	Aoki et al., 2008
	CSDH	The CatK levels were increased while the Cystatin C levels were decreased when compared with normal controls, suggesting that CatK is highly relevant with the development of CSDH.	Tsutsumi et al., 2017
	Schizophrenia	The CatK expression was markedly upregulated in postmortem brains of patients suffering from schizophrenia who received long-term treatment with neuroleptics. This upregulation of CatK might contribute to the altered opioid levels in brains of schizophrenics probably through processing β-endorphin to release met-enkephalin.	Ko et al., 2006; Lendeckel et al., 2009
Cardiovascular system	Cardiac dysfunction	CatK deficiency are beneficial to cardiac dysfunction, including the obesity-associated cardiac hypertrophy, the pressure overload–induced cardiac hypertrophy, the diabetes-induced cardiac anomalies and the aging-induced cardiac dysfunction.	Hua et al., 2013a, b; Hua et al., 2015; Guo et al., 2017a
	MI	The CatK-deficient mice exhibited worsen post-MI cardiac function along with increased collagen deposition and fibrosis, enhanced cardiac cell death, and reduced cardiac cell proliferation than the wildtype controls.	Fang et al., 2019
	Atherosclerosis	The deficiency of CatK resulted in the reduced number of advanced lesions as well as decreased individual advanced plaque area but increased number of initial plaques in the CatK-deficient apoE–/– mice as compared with the CatK-intact apoE–/–.	Lutgens et al., 2006
Respiratory system	Lung fibrosis	The pulmonary fibroblast from CatK-deficient mice showed decreased cathepsin-mediated collagenolytic activity as compared with those from wildtype mice, whereas pulmonary fibroblast from patients with lung fibrosis exhibited enhanced CatK activity.	Bühling et al., 2004
Other organs and systems	Autoimmune diseases	The lack of CatK activity could affect the innate immune response to pathogen DNA by compromising TLR9 signaling in DCs, leading to the attenuated induction of T helper 17 cells without affecting the antigen-presenting ability of DCs.	Asagiri et al., 2008
	Physiological function of thyroid	CatK is expressed by the thyroid epithelial cells and secreted into the follicular lumen for mediating the extracellular proteolysis of the prohormone TG, which is the essential process for the thyroxine liberation.	Tepel et al., 2000; Friedrichs et al., 2003; Jordans et al., 2009
	Overweight/obese	The adipogenesis was enhanced by CatK overexpression but retarded after CatK deficiency. Body weight gained after high-fat diet was remarkably decreased in mice with either genetic knockout or pharmacological inhibition of CatK when compared with the controls.	Funicello et al., 2007; Yang et al., 2008