In general, the only major differences between the en-us, en-uk and most other english based localisations would be how its designed to handle various number formats ( for example dates, decimal seperators and so on ) and - and this is something you will likely need to take into account when coding the software - the french use commas for decimal points, the americans use MM DD YYYY rather than DD MM YYYY as the commonwealth uses, and so on. There's also minior spelling variations, but most would consider this inconsequential, unless its a specific localisation
In most cases, localisation tends to be for large changes in language (english vs french for example) rather than variations of the same language. Should you be designing for multiple languages wikipedia might be a good primer/starting point on the processes, and has various guides linked/cited
While in theory nasty things can happen if you mix up metric and imperial units - the mars climate orbiter is proof of that practically, if you plan and test properly I'd think no testing is needed outside the usual "will this constantly crash and piss off my customers, or did I miss something obvious, or is this leaking memory".
Treat it as you would any other software product, and you should be fine