Despite substantial evidence of definitive differences between the temporomandibular joint (TMJ) and appendicular joints, the TMJ has frequently been considered analogous to other joints thus moderating the identification and implementation of specific therapeutic, diagnostic and preventive strategies for its disorders. The known differences between appendicular and temporomandibular joints range from its ontology, development, function, organization, histology, and the pathogenesis and epidemiology of TMJ disorders. This symposium will compare and contrast the contemporary understanding on the differences between TMJ vs appendicular joints that point to potential precision driven therapies and diagnostics and propose future directions for continued discovery. It is expected that current understanding and future discoveries will further help dissect the complex and unique nature of TMJ function, organization, anatomy and cellular/molecular functions leading to implementation of novel and joint-specific therapeutic and regenerative approaches.