NFIC-mediated CaSR endocytosis defines a hyperactive TOMM20highCHGAhigh oxyphil cell state as a pathological driver of autonomous secondary hyperparathyroidism

Secondary hyperparathyroidism (SHPT) is a debilitating complication of chronic kidney disease. Its clinical management is frequently compromised by calcimimetic resistance, a refractory state primarily driven by the progressive downregulation of the membrane calcium-sensing receptor (CaSR). Despite the centrality of CaSR as a therapeutic target, the mechanisms governing its aberrant expression and membrane localization remain incompletely elucidated. Here, we generated a single-cell transcriptomic atlas of human parathyroid tissues from SHPT and primary hyperparathyroidism (PHPT) patients, uncovering a unique stromal-immune niche that is specifically induced by uremic stress in SHPT. Our dat