Tight junctions are complex structures that form a continuous barrier between epithelial cells, regulating the selective movement of solutes across tissues. Initially viewed as inert solute barriers, tight junctions are now understood to have significant physiological and biochemical roles. Key proteins, including claudins, are critical for defining tight junction selectivity. Claudins, named from the Latin "claudere" meaning "to close," are transmembrane proteins that regulate permselectivity, including size, electrical resistance, and ionic charge preference. Tight junctions are modeled as having two physiologic components: a system of charge-selective small pores (4 Å in radius) and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination. The first pathway is influenced by claudin expression patterns, while the second is likely controlled by different proteins and signals. Tight junctions are essential for maintaining electrical resistance and ion selectivity in epithelial tissues. The permeability of tight junctions is influenced by the composition of claudins, with different claudins affecting the barrier's properties. For example, claudin-2 increases permeability for small ions, while claudin-16 is involved in magnesium reabsorption. Mutations in claudin genes can lead to diseases such as hypomagnesemia hypercalcemia with nephrocalcinosis (HHNC) and autosomal recessive deafness. Claudins also play a role in cell adhesion and signaling, and their dysfunction can lead to various pathologies. The study of tight junctions has evolved significantly, with the discovery of claudins providing new insights into their structure and function. Claudins are involved in creating ion-selective pores and are critical for maintaining the barrier function of tight junctions. The two pathway model of tight junction permeability highlights the complexity of paracellular transport, with small pores and non-selective breaks contributing to overall permeability. Understanding the role of claudins and other tight junction proteins is essential for elucidating the physiological and pathophysiological functions of tight junctions.Tight junctions are complex structures that form a continuous barrier between epithelial cells, regulating the selective movement of solutes across tissues. Initially viewed as inert solute barriers, tight junctions are now understood to have significant physiological and biochemical roles. Key proteins, including claudins, are critical for defining tight junction selectivity. Claudins, named from the Latin "claudere" meaning "to close," are transmembrane proteins that regulate permselectivity, including size, electrical resistance, and ionic charge preference. Tight junctions are modeled as having two physiologic components: a system of charge-selective small pores (4 Å in radius) and a second pathway created by larger discontinuities in the barrier, lacking charge or size discrimination. The first pathway is influenced by claudin expression patterns, while the second is likely controlled by different proteins and signals. Tight junctions are essential for maintaining electrical resistance and ion selectivity in epithelial tissues. The permeability of tight junctions is influenced by the composition of claudins, with different claudins affecting the barrier's properties. For example, claudin-2 increases permeability for small ions, while claudin-16 is involved in magnesium reabsorption. Mutations in claudin genes can lead to diseases such as hypomagnesemia hypercalcemia with nephrocalcinosis (HHNC) and autosomal recessive deafness. Claudins also play a role in cell adhesion and signaling, and their dysfunction can lead to various pathologies. The study of tight junctions has evolved significantly, with the discovery of claudins providing new insights into their structure and function. Claudins are involved in creating ion-selective pores and are critical for maintaining the barrier function of tight junctions. The two pathway model of tight junction permeability highlights the complexity of paracellular transport, with small pores and non-selective breaks contributing to overall permeability. Understanding the role of claudins and other tight junction proteins is essential for elucidating the physiological and pathophysiological functions of tight junctions.