Studies of inherited disorders of mineral metabolism have revealed their aetiologies to involve receptors, intracellular signalling pathways, and transcription factors. This is illustrated by studies of hypercalcaemic and hypocalcaemic disorders which have elucidated roles of the calcium-sensing receptor (CaSR), a G-protein coupled receptor (GPCR), in calcium homeostasis. Thus, CaSR mutations resulting in loss-of-function or gain-of-function lead to familial hypocalciuric hypercalcemia (FHH), and autosomal dominant hypocalcaemia (ADH), respectively. CaSR mutations are detected in ~65% of FHH and ~70% of ADH patients, referred to as FHH1 and ADH1, respectively. Studies have revealed genetic heterogeneity and defined two additional FHH types (FHH2 and FHH3), and another type of ADH (ADH2). FHH2 and ADH2 are due to loss- and gain-of-function mutations of G-protein subunit α11 (Gα11), respectively, and are found in <1% of FHH and ADH patients who do not have CaSR mutations. FHH3 is due to loss-of function mutations affecting adaptor protein-2 sigma subunit (AP2σ), encoded by AP2S1. AP2, a hetrotetrameric complex, is involved in clathrin-mediated endocytosis and AP2σ mutations, which are found in >20% of FHH patients who do not have CaSR or Gα11 mutations, impair CaSR internalisation and result in reduced CaSR signalling via a non-canonical endosomal pathway. These studies have provided new insights into GPCR signalling and trafficking, and advanced therapeutic options, such as CaSR allosteric modulators, for disorders of calcium metabolism. Finally, GWAS of serum adjusted-calcium, phosphate, 25-hydroxyvitamin D, and alkaline phosphatase in 274,547 to 403,674 individuals from the population-based UK Biobank (UKB) cohort, with cross-trait analysis have enabled assignment of 128 novel genes to physiological axes corresponding to parathyroid hormone (PTH) synthesis, fibroblast growth factor-23 (FGF23) secretion and bone mineralisation, and vitamin D metabolism. Thess studies have defined the genetic architecture of mineral metabolism, and established a framework for mechanistic discovery and therapeutic development for mineral disorders.