SLC4A11 Revisited: Isoforms, Expression, Functions, and Unresolved Questions.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• The SLC4A11 gene encodes a membrane transporter crucial for corneal endothelium function and implicated in diseases like congenital hereditary endothelial dystrophy and cancer.
• Existing data on SLC4A11 expression, variants, and functions are inconsistent, necessitating a comprehensive review.

Purpose of the Study:

• To systematically review and consolidate current knowledge on SLC4A11 transcript diversity, expression patterns, and functional roles.
• To clarify the impact of SLC4A11 complexity on disease mechanisms, particularly in the corneal endothelium and cancer.

Main Methods:

• Systematic review of existing literature on SLC4A11 gene and protein.
• Analysis of transcript variants, tissue expression data, and functional studies.
• Evaluation of pathogenic mutations and their cellular consequences.

Main Results:

• SLC4A11 exhibits significant transcript and isoform diversity, influencing its expression and function.
• The transporter's roles extend beyond bicarbonate transport to include ammonia, pH, and lactate transport, cellular stress, and adhesion.
• Pathogenic mutations disrupt SLC4A11 maturation, localization, or activity, leading to corneal diseases and potentially influencing cancer metabolism.

Conclusions:

• SLC4A11's complex biology, including its isoforms and diverse functions, is critical for understanding its role in health and disease.
• Further isoform-specific studies are needed to address methodological challenges and clarify SLC4A11's precise functions, especially in cancer metabolism.
• This review highlights research gaps and provides a foundation for future SLC4A11 investigations.