The UsePortNumber setting is one of the AppSettings that is contained in the web.config file.

By default http websites run on port 80. In some cases an install may want to run on an alternative port, perhaps as that port is already in use e.g. use an alternative port such as 8080, giving a url of http://www.mysite.com:8080 . Another scenario is creating a DotNetNuke website via the starterkit. As this is intalled into visual studio.net, starting the site will invoke the built-in webserver (called Cassini) rather than IIS. Cassini will create a random port for the website (and store this port number in the vs.net project settings file) to start the site resulting in a url such a http://www.mysite.com:3691

If your site require the use of a port other than 80, then setting UsePortNumber to true will tell DotNetNuke to retain the port number and use it to determine the site request. Sites can then add a Portal alias to reflect this setup e.g. mysite.com:8080

Note: This is not necessary if you site imply wants to use SSL, as DotNetNuke will detect this and convert the protocol from HTTP to HTTPS as necessary.