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In your case, chipset first (lower-end Ryzen chipsets don’t support PCIe Gen 4 on all slots), which will dictate cost somewhat.
Then slot configuration and spacing; will the board physically and electrically support the cards/drives you’ll want to use? This will also dictate form factor (ATX/ITX/mATX).
You mention the system will be on 24/7; will it be a server? If so, Asrock Rack make a great mini range of server boards for your CPU platform, with proper out-of-band management etc and no budget wasted on stupid flashing RGB LEDs or Darth Vader looking heatsinks.
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Cheers and @Velocio
Machine will mainly be used as Plex server with NAS with various other stuff like radarr, sonarr, etc and a few other similar always-on stuff. Lots of drives so will be in an ATX case.
It will occasionally also be used for a bit of office and other random shit (through remote desktop). Ideally it would be two machines but I don't really have the space for that.
I don't anticipate changing much on it over the years. It won't be used for gaming/have a graphics card and, given it will likely be in a cupboard or similar, I won't be plugging much in.
The ASRock Rack ones sound interesting but I'm struggling to find much about them (or many places selling them in the UK).
Motherboards? I normally treat them like wine in a restaurant and buy the second cheapest but I feel that I should actually put some thought into it. There's a huge array of prices but I can't really see what the difference is.
Beyond the obvious (memory capacity, type of USB, number of ports, etc) what should I be looking for? Will be paired with Ryzen 5600G, no intention of overclocking but it will be on 24/7.