We hypothesize that the specific binding of DRB1*13:02 to cathepsin S (Davenport et al., 1995) might lead to the production of antibodies that may, ultimately, limit the availability of cathepsin S, thus exerting an indirect neuroprotective effect, especially in conditions where cathepsin S seems to play a detrimental role, as in aging, neuroinflammatory conditions, traumatic brain injury, and other brain diseases, such as Alzheimer's disease (Shi et al., 1994; Munger et al., 1995; Lemere et al., 1995) and amyotrophic lateral sclerosis (Wendt et al., 2008). Here, CTSS is linked to early-onset autosomal dominant Alzheimer disease.