Valproate, PBA, and Li reduce intracellular retention of D469del-COMP, chondrocyte loss, and chondrocyte inflammation in D469del-COMP hind limbs. Tibias from P28 mice were collected and analyzed using H&E and TUNEL staining, human COMP and YM1 immunostaining. Valproate, PBA, and Li was administered from birth to P28. The D469del-COMP growth plate was disorganized (E) compared to control (A). Valproate and PBA treatment improved growth plate organization (I, M), The Li-treated D469del-COMP growth plate was more disorganized and appeared to have fewer cells (Q). Intracellular retention of D469del-COMP is decreased by drug treatments (J, N, and R) compared to untreated D469del-COMP mice (F). TUNEL and YM1 immunostaining is reduced by valproate, PBA, and Li therapy at 28 days (K, O, and S compared to G, and L, P, T compared to H). Bar = 100 μm.