functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption. Am J Physiol Regul Integr Comp Physiol 307: R1381-R1395, 2014. First published October 22, 2014 doi:10.1152/ajpregu.00033.2014.-For adaptation to highsalinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes. cartilaginous fish; kidney; osmoregulation; transporters; urea BODY FLUID REGULATION is essential for all organisms to survive in their respective habitats, including freshwater (FW), seawater (SW), and terrestrial environments. It is well known that teleost fish regulate their plasma Na ϩ and Cl Ϫ concentrations and osmolality at levels about one-third of SW. Meanwhile, cartilaginous fishes (sharks, skates, rays, and chimaeras) have adopted a unique osmoregulatory strategy for adaptation to the high-salinity marine environment. Cartilaginous fishes control plasma ions to levels approximately one-half of surrounding SW while they store high concentrations of the nitrogenous compound urea as an osmolyte (the so-called "ureosmotic strategy"). As a result, their body fluids are slightly hyperosmotic to surrounding SW (for instance, plasma osmolality of houndshark is 1,000 mosmol/kg H 2 O in SW of 988 mosmol/kg H 2 O; Ref. 53), and thus cartilaginous fishes do not typically suffer dehydration even in the high-osmolality SW environment. To maintain high concentration of urea in the body, urea production by the ornithine urea cycle (OUC) is essential. Investigations on the OUC enzymes have proved that the liver is the primary organ f...