Calcium pyrophosphate deposition disease (CPPD) involves the formation and deposition of calcium pyrophosphate dihydrate (CPP) crystals within articular cartilage (chondrocalcinosis) and periarticular tissues. CPP crystals are generated when excess inorganic pyrophosphate (PPi), produced by chondrocytes via the ectoenzyme ENPP1 and transported extracellularly by the ANK transporter, combines with calcium in the pericellular matrix. Unlike monosodium urate crystals in gout, CPP crystals are rhomboid-shaped and exhibit weakly positive birefringence under polarized light microscopy (compared to strong negative birefringence in gout — a critical diagnostic distinction). Crystal deposition triggers acute inflammation through NLRP3 inflammasome activation in synovial macrophages, leading to IL-1-beta release, neutrophil recruitment, and acute synovitis clinically indistinguishable from gout or septic arthritis (pseudogout). CPPD preferentially affects the knee (most common), wrist (especially the triangular fibrocartilage), and pubic symphysis. Underlying metabolic conditions that increase PPi or calcium levels predispose to CPPD: hyperparathyroidism, hemochromatosis, hypomagnesemia, hypophosphatasia, and Wilson disease. The NP must differentiate CPPD from gout, septic arthritis, and rheumatoid arthritis, as management differs significantly.