Thus, future studies are warranted to clarify the complex interplay between TNF, PGRN, and their receptors in the pathogenesis of arthritis and bone remodeling, which not only will improve our understanding of TNFR signaling in the pathogenesis of these musculoskeletal disorders but also may lead to innovative therapies via selective targeting of distinct TNFR pathways. Here, GRN is linked to arthritic joint disease.