Accumulation of Δe14-PTHR in cells expressing PTHR from different tissues, we propose, inhibits signaling and function of the full-length receptor and could explain PTH resistance in some cases of pseudohypoparathyroidism and perhaps in other forms of PTH or PTH-related protein (PTHrP) resistance of unknown origin. The gene discussed is PTHLH; the disease is pseudohypoparathyroidism.