In diabetic nephropathy, the weakening of CTSB activity leads to reduced degradation of the basement membrane, resulting in excessive deposition of extracellular matrix components, further exacerbating the thickening of the glomerular basement membrane, which leads to glomerular filtration dysfunction and inflammatory responses, thereby indirectly worsening diabetic nephropathy (23–26). Here, CTSB is linked to diabetic kidney disease.