Aligned with an interplay between cathepsin K activity and TLR9 activation in mouse models of bacteria-induced periodontitis, bone resorption is consistently associated with increased infiltration of immune cells (macrophages, T cells, and dendritic cells) and increased expression of TLRs (TLR4 and TLR9), autophagy proteins (transcription factor EB [TFEB] and microtubule-associated protein light chain 3 [LC3]) and inflammatory cytokines (interleukin [IL]1β, IL1α, IL6, or tumor necrosis factor alpha [TNFα]) in the periodontium. The gene discussed is CTSK; the disease is periodontitis.