K⁺-Cl⁻ co-transporter 2 (KCC2/SLC12A5) is a neuronal specific cation chloride co-transporter which is active under isotonic conditions, and thus a key regulator of intracellular Cl⁻ levels. It also has an ion transporter-independent structural role in modulating the maturation and regulation of excitatory glutamatergic synapses. KCC2 levels are developmentally regulated, and a postnatal upregulation of KCC2 generates a low intracellular chloride concentration that allows the neurotransmitters γ-aminobutyric acid (GABA) and glycine to exert inhibitory neurotransmission through its Cl⁻ permeating channel. Functional expression of KCC2 at the neuronal cell surface is necessary for its activity, and impairment in KCC2 cell surface transport and/or internalization may underlie a range of neuropathological conditions. Although recent advances have shed light on a range of cellular mechanisms regulating KCC2 activity, little is known about its membrane trafficking itinerary and regulatory proteins. In this review, known membrane trafficking signals, pathways and mechanisms pertaining to KCC2’s functional surface expression are discussed.

ķ ⁺ -Cl ^-共-转运蛋白2（KCC2 / SLC12A5）是一种神经元特异性阳离子氯化物共转运其等渗条件下是有效的，并因此细胞内氯的关键调节剂^-水平。在调节兴奋性谷氨酸能突触的成熟和调节中，它还具有独立于离子转运蛋白的结构作用。KCC2的水平受到发育调节，并且出生后KCC2的上调产生低的细胞内氯离子浓度，使神经递质γ-氨基丁酸（GABA）和甘氨酸通过其Cl-发挥抑制性神经递质的作用^。渗透通道。KCC2在神经元细胞表面的功能性表达是其活性所必需的，而KCC2细胞表面转运和/或内在化的损伤可能是一系列神经病理学状况的基础。尽管最近的进展揭示了调节KCC2活性的一系列细胞机制，但对其膜运输行程和调节蛋白知之甚少。在这篇综述中，讨论了与KCC2的功能性表面表达有关的已知膜运输信号，途径和机制。