These findings complement genetic evidence that CTSB variants associated with increased expression levels are protective against the disease and provides potential mechanistic support for the genetic interaction between CTSB and GBA. Beyond the direct genetic association, impaired catB expression or activity have also been reported in cellular or animal models associated with PD-risk factors like α-syn/SNCA, GBA, TMEM175 and LRRK2 [11–17, 71]. This evidence concerns the gene GBA1 and Parkinson disease.