Absence of evidence that Slc12a8 encodes a nicotinamide mononucleotide transporter

This Nature Metabolism Matters Arising challenged the claim that SLC12A8 had been established as a specific NMN transporter.

Schmidt and Brenner argued that prior genetic, pharmacological and kinetic evidence supported NMN dephosphorylation to nicotinamide riboside before cellular internalization and that the SLC12A8 data did not adequately demonstrate specific NMN transport.

The existence of this formal published disagreement means the Evidence Center should describe the NMN-transporter question as contested rather than settled.

• The authors disputed the evidence that SLC12A8 specifically transports NMN.
• They emphasized prior evidence supporting extracellular NMN dephosphorylation before cellular uptake.
• They argued that SLC12A8's known transporter annotation and available kinetic data did not establish the proposed role.
• The article directly responds to Grozio et al. 2019.

• This is a Matters Arising critique rather than a standalone intervention study.
• It evaluates and interprets existing mechanistic evidence.
• Later experimental work may further refine the transporter question.
• The article does not determine human clinical efficacy or oral supplement outcomes.