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I upgraded my V4 with an RPi5 a while ago (as have others); I shared my experiences in this thread: Zynthian 4 upgraded with Raspberry pi 5! - #18 by ricard

My opinion though it that it is absolutely necessary to make adjustments to the case in terms of filing up the holes for the LAN and USB ports, because apart from having been swapped between the two RPi version, they are not in the exact same position either.

Also, just using a GPIO extender to make room for a cooling block on the RPi5 means that there is no mechanical mounting of the ADC/DAC board; I opted to use two angle brackets to attach it to the rear of the case. I know others have gone just with the GPIO expander which may be fine, but I still think it is a bit mechanically dodgy to rely on just the connector (albeit a 40-pin one) to hold the ADC/DAC board.

I used a passive off-the-shelf cooling block, which thermally connects to the rear of the case using strips of thermal pads. My opinion though is that if you want to run your Zynthian at a constant high CPU load that that is not sufficient; it will get hot and start throttling down. I tend not to do that; I’m using the additional power of the RPi5 to get more voices and lower latency for sure (and to get access to Osirus), but for the music I do, I don’t need to run it at max load constantly, so this is not an issue for me.

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