Target intelligence / Profile preview

Solute carrier family 26 member 4 (Pendrin) (SLC26A4)

Target
SLC26A4
Molecular classification
Transporter, Solute carrier family 26 (SLC26), Anion exchanger
01

Overview

Solute carrier family 26 member 4 (SLC26A4), commonly known as pendrin, is a transmembrane protein that functions as an electroneutral anion exchanger, primarily mediating the transport of chloride, bicarbonate, and iodide across cell membranes. It is expressed in specialized epithelial cells within the inner ear, thyroid gland, kidney, and respiratory tract, where it plays a vital role in maintaining ion balance, pH, and fluid homeostasis. Mutations in the SLC26A4 gene are a leading cause of hereditary hearing loss, manifesting as Pendred syndrome—characterized by sensorineural deafness and thyroid goiter—or non-syndromic enlarged vestibular aqueduct. In the kidney, pendrin contributes to blood pressure regulation by mediating salt reabsorption in the cortical collecting duct, making it a potential target for novel diuretic therapies to treat hypertension and edema. Additionally, pendrin is significantly upregulated in inflammatory airway diseases such as asthma and cystic fibrosis, where it promotes mucus production and airway surface liquid depletion, positioning it as a promising therapeutic target for respiratory conditions.

Other names
PendrinPDSSolute carrier family 26 member 4Sodium-independent chloride/iodide transporter
02

Mechanism of action

Inhibition of anion exchange activity (primarily Cl-/HCO3- or Cl-/I- transport) to modulate fluid volume, pH, or salt excretion.

03

Biological functions

Anion exchange (Chloride/Bicarbonate)Anion exchange (Chloride/Iodide)Anion exchange (Chloride/Thiocyanate)pH regulationFluid homeostasisSalt reabsorptionIodide efflux
04

Disease associations

Pendred syndromeNon-syndromic hearing loss (DFNB4)Enlarged vestibular aqueduct (EVA)HypertensionAsthmaCystic fibrosisChronic obstructive pulmonary disease (COPD)
05

Safety considerations

Ototoxicity (potential for hearing loss if inhibited during development)Thyroid dysfunction (goiter or hypothyroidism due to impaired iodide transport)Metabolic alkalosis (due to impaired bicarbonate secretion in the kidney)Electrolyte imbalance
06

Interacting drugs

PDSinh-A01

4 more in the full profile.

07

Biomarkers

SLC26A4 gene mutations (e.g., p.H723R, IVS7-2A>G)Urinary bicarbonate levelsUrinary pHThyroid-stimulating hormone (TSH) levelsThyroxine (T4) levelsHearing thresholds (audiometry)Vestibular aqueduct diameter (imaging)

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